Gemcitabine Hydrochloride, Nab-Paclitaxel, PEGPH20, and Rivaroxaban in Treating Patients with Stage III-IV Pancreatic Cancer That Cannot Be Removed by Surgery

Status: Active

Description

This pilot phase II trial studies the side effects and how well gemcitabine hydrochloride, nab-paclitaxel, pegylated recombinant human hyaluronidase PH20 (PEGPH20), and rivaroxaban work in treating patients with stage III-IV pancreatic cancer that has spread to other places in the body (metastatic) and cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. PEGPH20 may stop the growth of tumor cells by breaking down hyaluronan, a tissue component needed for cell growth. However, PEGPH20 is also associated with an increased risk for blood clots. Rivaroxaban is a blood thinner that may help prevent blood clots. Giving gemcitabine hydrochloride, nab-paclitaxel, PEGPH20, and rivaroxaban together may work better in treating pancreatic cancer.

For patients with locally advanced disease, no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of PDAC is permitted; for patients with metastatic disease, prior treatment for non-metastatic disease with 5-fluorouracil (5-FU) or gemcitabine administered as radiation sensitizer, or as a cytotoxic therapy, in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no >= grade 2 treatment-related toxicities are present

Karnofsky performance status >= 70%

Life expectancy >= 3 months

A negative serum pregnancy test, if female of reproductive potential

Total bilirubin =< 1.5 times upper limit of normal (ULN) (performed within 14 days prior to day 1)

Platelet count >= 100,000 plt/mm^3 (performed within 14 days prior to day 1)

Hemoglobin >= 9 g/dL (performed within 14 days prior to day 1)

Prothrombin time (PT)/international normalized ratio (INR) within normal limits (+/- 15%) or within therapeutic range if on warfarin (performed within 14 days prior to day 1)

Partial thromboplastin time (PTT) within normal limits (+/- 15%) (performed within 14 days prior to day 1)

For men and women of reproductive potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study; effective contraceptive methods consist of prior sterilization, intra-uterine device, oral or injectable contraceptives, and/or barrier methods; abstinence alone is not considered an adequate contraceptive measure for the purposes of this study

Exclusion Criteria

Known central nervous system involvement or brain metastases

New York Heart Association class III or IV cardiac disease or myocardial infarction within the past 12 months

History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer or curatively-treated cervical carcinoma in-situ

History of transient ischemic attack (TIA) or cerebrovascular accident (CVA)

Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that may render the subject at high risk for treatment complications

Other unspecified reasons that, in the opinion of the investigator, make the subject unsuitable for the study

Inability to comply with study and follow-up procedures as judged by the investigator

Patients receive pegylated recombinant human hyaluronidase PH20 intravenously (IV) over 10-12 minutes on days 1, 4, 8, 11, 15, and 18, nab-paclitaxel IV over 30 minutes on days 2, 8, and 15, and gemcitabine hydrochloride IV over 30 minutes on days 2, 8, and 15 of cycle 1. Patients then receive PEGPH20 IV over 10-12 minutes, nab-paclitaxel IV over 30 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 of subsequent cycles. Patients receive rivaroxaban orally (PO) twice daily (BID) on days 1-21 and once daily (QD) on days 22-28 of cycle 1 and QD on days 1-28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 3 months thereafter.